Though clearly beneficial, the use of methadone during pregnancy remains controversial partly due to the large percentage of newborns having signs of opioid withdrawal requiring medical intervention and extended hospitalization. A newly approved medication, Buprenorphine, produces only a mild abstinence syndrome following abrupt withdrawal. Promising preliminary data from a double-blind randomized trial at the Johns Hopkins School of Medicine (JHUSOM) suggest that buprenorphine use results in improved birth outcomes and less neonatal abstinence syndrome (NAS) relative to methadone. The current randomized, parallel group study will be the first multi-site trial to assess the efficacy of buprenorphine for reducing NAS relative to methadone. The Wayne State University (WSU) Site proposes to participate in the multi-site trial lead by JHUSOM involving six U.S. and two international sites. The Substance Abuse Research division (SARD) at WSU has brought together a multi-disciplinary group trained in addiction medicine, psychiatry, pediatrics, obstetrics, neonatology, and controlled clinical trials with the professional expertise to provide comprehensive care for the subjects and rigorous scientific integrity for the study. At this site subjects randomized to equivalent optimal doses of methadone (n=20) or buprenorphine (n=20) will be followed through pregnancy. Treatment groups will be compared on the primary outcome measures of peak total NAS score; number of neonates treated for NAS; total amount of anti-withdrawal medication given to neonates treated for NAS; physical birth parameter of head circumference; and neonatal length of hospital stay. Secondary neonatal/fetal outcome measures include other physical, behavioral and safety parameters. Secondary maternal outcomes include treatment retention, drug use, medication safety, psychosocial functioning and dose adequacy. Unique to this site, a pilot study will be conducted in which maternal salivary cortisol levels during pregnancy and labor and neonatal stressed (after heel prick blood draw) and unstressed salivary cortisol levels will be obtained. In addition, the WSU site also proposes to extend neonatal follow up to 6 months. The WSU site has unique expertise and experience (including participation in the NIDA Clinical Trial Network) and resources to contribute to this new potential network designed to conduct pharmacotherapy trials for substance abusing and dependent individuals in a difficult to recruit population (i.e., pregnant women). The Wayne State site also proposes to participate in the NICU (Neonatal Intensive Care Unit) Network Neurobehavioral Scale (NNNS) as a secondary outcome measure in collaboration with the Providence, Rhode Island site and the lead site (Johns Hopkins).